Contents:
Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 1 | 277 | 1p36.33 | TNFRSF4 | TNF receptor superfamily member 4 | |
| Mouse | 1 | 272 | 4 87.68 cM | Tnfrsf4 | tumor necrosis factor receptor superfamily, member 4 | |
| Rat | 1 | 271 | 5q36 | Tnfrsf4 | TNF receptor superfamily member 4 | |
| Previous and Unofficial Names |
| ACT35 | CD134 | TXGP1L | MRC OX40 | OX40L receptor | Tax-transcriptionally activated glycoprotein 1 | tumor necrosis factor (ligand) superfamily, member 4 | tumor necrosis factor receptor superfamily |
| Database Links |
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| Alphafold | P43489 (Hs), P47741 (Mm), P15725 (Rn) |
| ChEMBL Target | CHEMBL3989383 (Hs) |
| Ensembl Gene | ENSG00000186827 (Hs), ENSMUSG00000029075 (Mm), ENSRNOG00000020106 (Rn) |
| Entrez Gene | 7293 (Hs), 22163 (Mm), 25572 (Rn) |
| Human Protein Atlas | ENSG00000186827 (Hs) |
| KEGG Gene | hsa:7293 (Hs), mmu:22163 (Mm), rno:25572 (Rn) |
| OMIM | 600315 (Hs) |
| Pharos | P43489 (Hs) |
| RefSeq Nucleotide | NM_003327 (Hs), NM_011659 (Mm), NM_013049 (Rn) |
| RefSeq Protein | NP_003318 (Hs), NP_035789 (Mm), NP_037181 (Rn) |
| UniProtKB | P43489 (Hs), P47741 (Mm), P15725 (Rn) |
| Wikipedia | TNFRSF4 (Hs) |
| Natural/Endogenous Ligands |
| OX-40 ligand {Sp: Human} |
| Adaptor proteins (Human) |
| TRAF1, TRAF2, TRAF3, TRAF5 |
Download all structure-activity data for this target as a CSV file 
| Antibodies | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Antibody Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||
| The anti-OX40 monoclonal antibodies (mAbs) GSK3174998, BMS-986178 [4] and MEDI6469 [2] are examples that are in active clinical development (as of Feb. 2021) as potential immuno-oncology agents [1]. Blocking OX40 signalling is predicted to enhance anti-tumour T cell immunity. | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Binding Ligands | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immunopharmacology Comments |
| The OX40/OX40L pair is involved in late T-cell costimulatory signalling and both are transiently expressed following antigen recognition. Blocking OX40/OX40L is reported to prevent the development of disease in in vivo autoimmune and inflammatory disease models [9]. Amgen and Kyowa Kirin are partnering on the latter's anti-OX40 antibody KHK4083, for moderate to severe atopic dermatitis [6]. If successful this partnership could pursue KHK4083's potential in other inflammatory diseases [3,7]. Anti-OX40 mAbs are also being investigated for neoadjuvant activity, as a mechanism to enhance anti-tumour T cell activity in cancer patients [2]. |
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References
1. Cebada J, Perez-Santos M, Bandala C, Lara-Padilla E, Herrera-Camacho I, Rosas-Murrieta NH, Millán-Pérez Peña L, Monjaraz E, Flores A, Anaya-Ruiz M. (2021) OX40 agonists for cancer treatment: a patent review. Expert Opin Ther Pat, 31 (1): 81-90. [PMID:32945223]
2. Duhen R, Ballesteros-Merino C, Frye AK, Tran E, Rajamanickam V, Chang SC, Koguchi Y, Bifulco CB, Bernard B, Leidner RS et al.. (2021) Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells. Nat Commun, 12 (1): 1047. [PMID:33594075]
3. Furihata K, Ishiguro Y, Yoshimura N, Ito H, Katsushima S, Kaneko E, Shimabe M, Mukai M, Watanabe R, Morishige T. (2021) A Phase 1 Study of KHK4083: A Single-Blind, Randomized, Placebo-Controlled Single-Ascending-Dose Study in Healthy Adults and an Open-Label Multiple-Dose Study in Patients With Ulcerative Colitis. Clin Pharmacol Drug Dev, [Epub ahead of print]. DOI: 10.1002/cpdd.918 [PMID:33512065]
4. Gutierrez M, Moreno V, Heinhuis KM, Olszanski AJ, Spreafico A, Ong M, Chu Q, Carvajal RD, Trigo J, De Olza MO et al.. (2021) OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors. Clin Cancer Res, 27 (2): 460-472. [PMID:33148673]
5. Huseni M, Totpal K, Du C, Dalpozzo K, Zhu J, Rishipathak D, McNamara E, Jonshtone B, Hegde PS, Rhee I. (2014) Anti-tumor efficacy and biomarker evaluation of agonistic anti-OX40 antibodies in preclinical models. Journal for Immunotherapy of Cancer, 2 (Suppl 3): 105.
6. Nakagawa H, Iizuka H, Nemoto O, Shimabe M, Furukawa Y, Kikuta N, Ootaki K. (2020) Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to severe atopic dermatitis. J Dermatol Sci, 99 (2): 82-89. [PMID:32651105]
7. Papp KA, Gooderham MJ, Girard G, Raman M, Strout V. (2017) Phase I randomized study of KHK4083, an anti-OX40 monoclonal antibody, in patients with mild to moderate plaque psoriasis. J Eur Acad Dermatol Venereol, 31 (8): 1324-1332. [PMID:28556418]
8. Song Y, Margolles-Clark E, Bayer A, Buchwald P. (2014) Small-molecule modulators of the OX40-OX40 ligand co-stimulatory protein-protein interaction. Br J Pharmacol, 171 (21): 4955-69. [PMID:24930776]
9. Webb GJ, Hirschfield GM, Lane PJ. (2016) OX40, OX40L and Autoimmunity: a Comprehensive Review. Clin Rev Allergy Immunol, 50 (3): 312-32. [PMID:26215166]
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